Melatonin is a natural hormone found in all living animals. It can be taken as a supplement and you can find it in common foods (listed below)! Melatonin may be useful in treating COVID-19 infections and Long COVID.
Research shows melatonin can help treat different viral infections (Boga et al. 2012). Melatonin improves immune cell function while it suppresses harmful inflammatory cytokines such as tumor necrosis factor a (TNF-a), interferon (IFN)-a, interleukin (IL)-6 and IL-8 (discussion Lempesis et al. 2024).
Scientists speculate that the higher levels of melatonin in children may help protect them from COVID-19 (Muhammad et al. 2023). The levels of this hormone decline over the life span.
In people infected with COVID-19, taking melatonin reduced coughing, decreased fatigue, increased sleep quality, and accelerated recovery time. Severely ill patients using melatonin had reduced thrombosis, sepsis, and mortality rate. (Faridzadeh et al. 2022, Lempesis et al. 2024). Melatonin helps heal mitochondrial dysfunction in COVID-19 (Lempesis et al. 2024).
History: Melatonin has been used to treat other viral infections like respiratory syncytial virus (RSV).
Mechanisms:
RSV activates toll-like receptor (TLR3) which promotes nuclear factor kappa B (NF-κB) activity. NF-κB up-regulates inflammatory cytokines.
Melatonin inhibits NF-κB which decreases inflammation (Boga et al. 2012).
In case of viral attack or other cellular damage, cells can be preprogrammed to die (apoptosis) to help protect the organism. Dead cells are safely cleaned up by mechanisms such as autophagy, which degrades viruses while recycling old cell parts (Chen et al. 2023). Melatonin can help modulate both apoptosis and autophagy in viral infections (discussion in Boga et al. 2012).
People with mild cognitive impairment (MCI) who took 3-24 mg melatonin had significantly improved cognitive performance, less depression, and higher quality of sleep/wake rhythm (Cardinali et al. 2012).
Melatonin may improve depression by regulating biological systems. It modulates the creation of new neurons (neurogenesis), the antioxidant system, programmed cell death (apoptosis), and inflammation (Kholghi et al. 2022).
Melatonin interacts with the sympathetic nervous system (SNS) to reduce anxiety. It may slow down or prevent SNS activation since it enhances α-aminobutyric acid (GABA) (great chart in Repova et al. 2022). GABA inhibits several pathways that lead to SNS activation.
The sympathetic nervous system (SNS) is activated during stressful or dangerous situations. It prepares the body to fight, flee or freeze. When the SNS is activated it can contribute to acute and chronic stress and in anxiety. The autonomic nervous system, including the SNS, is dysregulated in different anxiety disorders.
In addition, melatonin helps mute the actions of glucocorticoids in many tissues including the brain. This reduced neurotoxicity in rats, suppressed their anxiety like behavior, and decreased corticosterone levels (discussion Repova et al. 2022).
Dosages of 9-15 mg melatonin for 10 days improved mood, decreased anxiety levels, and improved quality of life while decreasing cortisol levels in people who had fibromyalgia (Castaño et al. 2019).
Melatonin reduces inflammatory chemical markers caused by COVID-19 and may tamp down the excessive immune response that fuels harmful cytokine storms (Bahrampour et al. 2020, Faridzadeh et al. 2022). Inflammatory markers are chemicals like C-reactive protein (CRP) that detect or measure the level of inflammation in the body. Melatonin is twice as effective as the antiviral drug remdesivir or the biologic arthritis treatment tocilizumab (Castle et al 2021).
Melatonin is cytoprotective, which means it helps protect cells against harmful agents and anticancer. It inhibits tumor formation at all stages through membrane-independent and membrane-dependent mechanisms. This natural hormone has anti-inflammatory, antioxidant, and immunostimulant effects (Boga et al. 2012, Cardinali et al. 2022, Faridzadeh et al. 2022, Lempesis et al. 2024). It can also neutralize the harmful reactive oxygenated species (ROS) initiated by infections (discussion in Muhammad et al. 2023).
Viral infections can cause a shift in the way cells obtain energy. Normally, the healthy cell makes energy in the mitochondria using oxidative phosphorylation. This is the most efficient way to make energy. However, viruses and cancer can cause cells to create energy using glycolysis which occurs in the cytoplasm. This is known as the Warburg effect.
Why is the Warburg effect bad you ask? The Warburg effect generates energy in the cytoplasm. Energy made in the cytoplasm increases inflammation.
In the Warburg effect, cells use aerobic glycolysis to make most or all of their energy. Basically, glucose (sugar) is converted into two pyruvates and energy. Since this occurs in the cytoplasm, it causes an increase in cytoplasmic pyruvate, which increases hypoxia-inducible factor-1a (HIF-1a), NF-?B and other transcription factors promoting inflammation. This process is accelerated in tumour or virus affected cells (Vaupel et al. 2021).
Melatonin reverses the Warburg effect which reduces inflammation (Tian et al. 2021, Cardinali et al. 2022).
Glucose (a 6 carbon sugar) + 2 NAD (energy carrying molecules) + 2 ADP +2 inorganic phosphates (Pi) + 2 pyruvate (3C) + 2 NADH (energy carrying molecules) + 2 H+ + 2 net ATP (energy molecule).
Older people (557 people 61-77 years old) who ate foods high in melatonin had greater life satisfaction, a decrease in cognitive impairment (they could think better), and higher psychoemotional state (higher quality of life) (Borisenkov et a. 2024).
★ Pistachios: 233,000 ng/g dry weight
★ Roasted coffee beans: 9,600 ng/g dry weight
Brewed coffee: 9,600 ng/g per 50 mL (240 mL in 8 oz)
★ Mushrooms, including common white and brown cultivated mushrooms: 4,300-6,800 ng/g dry weight
★ Sprouted lentils: 1,089 ng/g dry weight
★ Black and red rice: 182-212 ng/g dry weight
★ Wheat: 125 ng/g dry weight
★ Oats: 91 ng/g dry weight
★ For a complete list of melatonin naturally occurring in foods see Table 1 Meng et al. 2017.
Precaution: most researchers believe that melatonin is safe for short term use and for use as an antiviral (Lempesis et al. 2024). However, it is a hormone and has been mostly studied in how it affects sleep. Trails are small and scientists are not sure about its effects on multiple organ systems. Melatonin can have side effects which include headache, daytime sleepiness, nausea, dizziness and more (Tuft et al. 2023).
Cytokine storm: the body reacts to a threat (such as a viral or bacteria infection or an autoimmune reaction) by rapidly dumping cytokines into the blood. This causes a severe immune reaction that can be life threatening. Symptoms include inflammation, fever, fatigue and nausea in mild causes and multiple organ failure in extreme cases.
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This information is for informational purposes only and does not constitute medical advice, diagnosis, or treatment.
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